UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelium-dependent relaxations are achieved by a combination of endothelium-derived prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mechanisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcholine (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and distal mesenteric arteries of the rat. The contributions of PGI2, NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N omega-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethacin, and KCl in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expression of endothelial No synthase (eNOS) was examined by both immunostaining and immunoblotting. The contribution of PGI2 was negligible in three different-sized blood vessels. The contribution of NO was most prominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was significantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesenteric arteries. These results indicate that the importance of EDHF increases as the vessel size decreases in endothelium-dependent relaxations in the rat mesenteric circulation.
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PMID:The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. 894 85

To elucidate pathophysiological alterations in vascular relaxation in rats with chronic heart failure (CHF), guanosine 3',5'-cyclic monophosphate (cGMP)- and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated vasorelaxations in pulmonary artery (PA) and thoracic aorta (TA) of rats were examined 12 wk after coronary artery ligation. Acetylcholine (ACh)-induced relaxation was attenuated in endothelium-intact segments of both arteries, whereas sodium nitroprusside-induced relaxation was attenuated only in endothelium-intact TA segments of rats with CHF. Vasorelaxations elicited by isoproterenol and NKH-477, a water-soluble forskolin analogue, were diminished mainly in PA segments of the CHF rat. NG-nitro-L-arginine methyl ester (L-NAME)-induced decrease in cGMP level was less in endothelium-intact TA segments of the rat with CHF (0.20 +/- 0.06 vs. 0.99 +/- 0.26 pmol/mg protein in control), suggesting that basal nitric oxide (NO) production is reduced in CHF. Treatment with L-NAME attenuated the isoproterenol-induced relaxation only in endothelium-intact TA segments in control rats but not in CHF rats. The results suggest that both cGMP- and cAMP-mediated relaxations are impaired in CHF, and a reduction of NO synthesis, presumably in endothelial cells, plays a significant role in pathophysiological alterations in vessels of rats with CHF.
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PMID:Impairment of cGMP- and cAMP-mediated vasorelaxations in rats with chronic heart failure. 899 78

In the present study we investigated the in vitro relaxant response of erectile tissue obtained from rabbits of different ages (3, 7 and 24 months) in order to detect the progression with age of cavernosal activity in response to substances acting via endothelium-dependent or -independent mechanisms. Noradrenaline induced a concentration-dependent contraction (0.1 microM-3 mM), with an increase in the contractility in the 24-month-old group. Acetylcholine produced a concentration-dependent relaxant effect in the three age groups, with a reduction of the maximal relaxant effect in older animals. ATP (10 microM-1 mM) and adenosine (10 microM-1 mM) induced a concentration-dependent relaxant effect that was higher in the older group. The presence of the NO2-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (0.1 mM) or of the P2-purinoceptor antagonist suramin did not affect ATP relaxation. Relaxation induced by sodium nitrite and nifedipine was reduced in older animals. In conclusion, aging selectively alters the in vitro responsiveness of rabbit erectile tissue. Purinergic system remains more active despite a decrease in the maximal endothelial cholinergic activity and the direct smooth muscle relaxant component.
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PMID:Characterization of in vitro relaxant mechanisms in erectile tissue from rabbits of different ages. 900 22

The effect of diatrizoate (Urografin325) on the cumulative dose-response curve of the vasodilatory response to acetylcholine was studied in the isolated perfused rat kidney (IPRK). The effect of 1-nitroarginine methyl ester (L-NAME) (10 mumol l-1) on the cumulative concentration-response curve of the vasodilatory response to acetylcholine and sodium nitroprusside was also studied. Acetylcholine is a vasodilator dependent on nitric oxide (NO) synthesis by the endothelium; sodium nitroprusside is a vasodilator not dependent on endogenous NO synthesis and L-NAME is an inhibitor of endogenous NO synthesis. The effect of L-NAME (10 mumol l-1) on the vasodilatory effect of diatrizoate which is observed in the presence of endothelin A receptor antagonist (BQ123, 10 mumol l-1) was also studied. In all experiments an infusion of angiotensin II (5 ng min-1) was maintained to increase the vascular tone of the preparation. Acetylcholine induced vasodilatation and the maximum increase in renal perfusate flow (RPF) was 17.0 +/- 1.7%, (p < 0.05). Diatrizoate (20 mgl ml-1 perfusate concentration) which induced a sustained fall in the RPF (-31.0 +/- 1.7%, p < 0.05) had no effect on the vasodilatory response to acetylcholine, and a similar increase in the RPF (17.8 +/- 2.2%, p < 0.05) was observed. In contrast, L-NAME (10 mumol l-1) completely abolished the vasodilatory effect of acetylcholine and produced instead a modest decrease in RPF by -5.0 +/- 1.7% (p < 0.05). The vasodilatory effect of sodium nitroprusside was not affected by L-NAME, confirming its selectivity as an inhibitor of endogenous NO synthesis in the IPRK. The maximum increase in the RPF induced by sodium nitroprusside was 23.1 +/- 2.0% (p < 0.05) in the absence of L-NAME and 21.2 +/- 2.2% (p < 0.05) in its presence. L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123. In the presence of BQ123 alone the RPF increased from 23.3 +/- 1.4 ml min-1 g-1 to 26.5 +/- 1.0 ml min-1 g-1 (p < 0.05). In the presence of L-NAME and BQ123 the RPF increased from 24.4 +/- 3.0 ml min-1 g-1 to 27.2 +/- 2.7 ml min-1 g-1 (p < 0.05). There was no difference between the two groups (p > 0.05). In conclusion, diatrizoate did not interfere with endothelium derived NO-dependent vasodilatation in the kidney. A reduced production of NO in the vascular endothelium induced by contrast media is unlikely to play any role in the pathophysiology of the increase in renal vascular resistance produced by these agents. The renal vasodilatation induced by diatrizoate is not dependent on endogenous production of NO.
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PMID:Effect of radiographic contrast media on endothelium derived nitric oxide-dependent renal vasodilatation. 913 41

1. The mechanism of the sustained acetylcholine-induced endothelium-dependent hyperpolarization (EDH) in intact rat small mesenteric arteries prestimulated with noradrenaline (10(-6) M) was investigated by means of the single microelectrode voltage-clamp method. 2. The vascular smooth muscle cells (VSMCs) in this preparation are poorly or even not coupled for the reasons that: (1) the mean input resistance Rlnp of the clamped vascular smooth muscle increases from 120 M omega under control conditions to 440 M omega after application of K+ channel blocking drugs, (2) the voltage relaxation after injection of hyperpolarizing currents has a monoexponential time course and is linearly dependent on Rlnp, and (3) voltage steps induced by current-clamp steps are not transferred to locations in the vascular musculature 120 microns apart from the current injecting microelectrode. 3. Sustained (> 5 min) application of ACh (10(-5) M) hyperpolarized the VSMCs by induction of a hyperpolarizing current. This effect was completely blocked by the inhibitor of the nitric oxide (NO) synthase L-NAME (10(-3) M) but not by the inhibitor of the soluble guanylate cyclase (sGCl) Methylene Blue (MB, 10(-4) M). 4. Application of the NO donor sodium nitroprusside (SNP, 10(-6) M) for more than 5 min mimicked the induction of the endothelium-dependent hyperpolarizing current in vessels with destroyed endothelium. The reversal potential of this current is dependent on the extracellular K+ concentration. The effect of SNP could also not be blocked by MB. 5. The blockers of ATP-dependent and Ca(2+)-dependent K+ channels, glibenclamide (Glb, 10(-5) M) and charybdotoxin (CTX, 5 x 10(-8) M), respectively, blocked a hyperpolarizing current in the VSMCs similar to the ACh- or SNP-induced current. 6. The isolated application of either Glb or CTX did not block the activation of the hyperpolarizing current by SNP. Only the combined administration of Glb and CTX blocked the SNP-induced current completely. 7. Our results suggest that in rat small mesenteric artery, ACh hyperpolarizes the VSMCs tonically by activating both ATP- and Ca(2+)-dependent K+ currents, only via release of NO from the endothelium without need for activation of the sGCl.
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PMID:Acetylcholine-induced K+ currents in smooth muscle cells of intact rat small arteries. 916 80

1. The double perfused mesentery was used to compare arterial and venous KCl- and acetylcholine (ACh)-induced responses in tissues taken from normotensive (WKY) and spontaneously hypertensive rats (SHR) in the presence or absence of inhibitors of nitric oxide (NO) synthase (NG-nitro-L-arginine (L-NOARG) and NG-nitro-L-arginine methyl ester (L-NAME)) and cyclo-oxygenase (indomethacin, mefenamic acid). 2. KCl (20 to 120 mM K+) caused concentration-dependent increases in arterial and venous perfusion pressures. The maximal arterial effects were significantly higher in the SHRs than in the WKY, with no differences in the venous pressor responses. 3. L-NAME and L-NOARG (100 microM) had no effect on the basal perfusion pressures in tissues from either WKY or SHRs, and mefenamic acid only induced a significant reduction of the basal perfusion pressures in the venous mesenteric vessels isolated from WKY. 4. L-NAME and L-NOARG (100 microM) potentiated the pressor responses to KCl to the same extent in the venous and arterial beds derived from WKY and SHR, while indomethacin and mefenamic acid (5 microM) only significantly decreased these responses in WKY. 5. Acetylcholine (ACh)-induced relaxations (1 nM to 10 microM) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant responses. 6. L-NAME (100 microM) inhibited ACh-induced relaxations in arterial and venous beds from both groups of rats. Mefenamic acid was without effect on ACh-induced relaxations in either the arterial or the venous beds from WKY and SHR. 7. In conclusion, the liberation of NO in the perfused mesenteric vasculatures requires an active tone and no dysfunction of NO synthase activity is functionally apparent in the mesenteries isolated from SHRs. The cyclo-oxygenase pathway is only implicated in the KCl-induced responses of tissues derived from WKY, but not in the vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.
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PMID:Comparison of the nitric oxide and cyclo-oxygenase pathway in mesenteric resistance vessels of normotensive and spontaneously hypertensive rats. 917 4

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated aortic tension and mean arterial pressure in renal hypertensive rats (RHR). Acetylcholine (ACh) relaxed aorta precontracted with norepinephrine from RHR significantly less than that from normotensive rats (NR) (Emax: 34.3% and 86.0%, respectively, P < 0.01). The ACh-induced relaxation was significantly enhanced by losartan (P < 0.05) and completely abolished by removal of endothelium or NG-nitro-L-arginine methyl ester (L-NAME). ACh lowered the mean arterial pressure slightly less effectively in RHR than in NR (6.8 and 13.0 mmHg, respectively, at 0.1 microgram/kg), whereas the depressor effect was reduced by L-NAME (-15.5 and 10.3 mmHg, respectively, at 0.1 microgram/kg), but rather enhanced by further treatment with losartan (9.9 (P < 0.05) and 17.3 mmHg, respectively, at 0.1 microgram/kg). Angiotensin II induced similar contractile and pressor responses in both RHR and NR, and these effects were significantly enhanced by L-NAME, except for the pressor effect in RHR. L-NAME induced a similar pressor response in RHR and NR (15.9 and 15.2 mmHg, respectively, at 0.1 mg/kg), the effect being decreased by pretreatment with losartan. Losartan induced a depressor response that was smaller in RHR than in NR (34.0 and 48.8 mmHg, respectively, at 0.3 mg/kg), and the response was significantly reduced by L-NAME. These results suggest that nitric oxide interacts with the renin angiotensin system to control the vascular tension and systemic arterial circulation in RHR.
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PMID:Interaction of nitric oxide and the renin angiotensin system in renal hypertensive rats. 919 1

Acetylcholine (ACh)-induced relaxation in the aortae precontracted with norepinephrine was significantly enhanced in the aortae from estrus (E) rats, compared with that in those from metestrus (D-1), diestrus (D-2) and proestrus (PE) rats. NG-Nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium-dependent relaxation in E rats. These results suggest that there is a difference in ACh-induced relaxation of the thoracic aorta during the sexual cycle of rats, and the relaxation is greatest in E of the sexual cycle; this may be due to a difference in nitric oxide synthesis in the endothelium in the sexual cycle.
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PMID:Acetylcholine-induced relaxation of rat aorta is greatest during estrus in the sexual cycle. 919 7

The goal of this study was to determine both the early and delayed effects of a brief (10-minute) coronary artery occlusion (CAO) and prolonged (5-day) reperfusion (CAR) on coronary endothelial function. Fourteen mongrel dogs were chronically instrumented to measure aortic and left ventricular pressures, wall thickness, and left circumflex coronary blood flow (CBF). Before CAO and during CAR, coronary vascular reactivity was investigated by 15-second CAO and subsequent reactive hyperemia (RH) and by the selective intracoronary infusion of acetylcholine (ACh, 10 micrograms/min) and bradykinin (BK, 2.5 micrograms/min), endothelium-dependent vasodilators, and sodium nitroprusside (SNP, 40 micrograms/min), an endothelium-independent vasodilator. CBF responses to ACh and BK began to increase after 6 hours of CAR, reached a peak after 1 to 2 days of CAR, and then subsided over the subsequent 4 days. After 1 day of CAR, compared with before CAO, enhanced CBF responses (P < .05), associated with increased coronary sinus oxygen content, were observed for-ACh (+66 +/- 20%), BK (+74 +/- 24%), and RH (+24 +/- 5%) but not SNP (-2 +/- 10%). Production of NO metabolites (nitrate and nitrite), measured as their coronary arteriovenous differencexCBF, was significantly increased after 1 to 2 days of CAR, both at baseline (153 +/- 56%) and during BK infusion (220 +/- 76%) (P < .05). Holding CBF at pre-CAO levels during the initial CAR period did not attenuate the delayed enhanced endothelial vasodilation to ACh and BK. However, NO blockade with intracoronary NG-nitro-L-arginine blocked the enhanced coronary vasodilation to ACh and BK. Thus, in contrast to previous studies, these data indicate that brief ischemic episodes induce delayed enhanced coronary endothelial function, which is delayed in onset and prolonged in duration. This can be explained by an upregulation of coronary vascular NO production, potentially involved in the mechanism of the delayed window of preconditioning.
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PMID:Delayed enhanced nitric oxide-mediated coronary vasodilation following brief ischemia and prolonged reperfusion in conscious dogs. 920 Oct 27

We report on the modulatory effects of chronic subcutaneous or oral estrogen and LY117018, a selective estrogen receptor modulator, on the release of nitric oxide in rings of rat aorta studied under isometric conditions. Dilator responses to acetylcholine (ACh; 10[8] to 10[-5] M) were obtained in phenylephrine (PE; 2 microM)-contracted aorta, and constrictor dose-response curves to PE (10[-8] to 10[-5] M) were generated before and after pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM), an inhibitor of nitric oxide synthase. Tissue segments were obtained from five groups of rats implanted with a subcutaneous pellet delivery system for 21 days: (1) male, (2) sham-operated placebo-treated female, (3) ovariectomized placebo-treated, (4) ovariectomized, 17beta-estradiol treated (0.5 mg/pellet) and (5) ovariectomized, progesterone (15 mg/pellet) and 17beta-estradiol (0.5 mg/pellet)-treated. Aortic rings from sham rats and ovariectomized rats receiving estrogen relaxed more to ACh (10[-6] to 10[-5] M) than did the rings from ovariectomized, progesterone plus estrogen-treated and male rats (P < .05). They were also characterized by a greater potentiation of the PE responses after L-NAME compared with male, progesterone plus estrogen-treated and ovariectomized rats (P < .05) and a similar sensitivity to PE. In addition, ACh-induced relaxation and L-NAME-induced potentiation of PE contractions in aortic rings from rats dosed orally with LY117018 were similar to responses of aortic rings from rats dosed orally with estrogen. These results demonstrate that chronically administered estrogen and LY117018 enhance the release of nitric oxide from endothelium in rat aortic rings.
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PMID:Estrogen and selective estrogen receptor modulator LY117018 enhance release of nitric oxide in rat aorta. 933 15

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